CLINICAL STUDY Diffusion abnormalities of the corpus callosum in patients receiving bevacizumab for malignant brain tumors: suspected treatment toxicity Stephen F. Futterer • Alexander J. Nemeth • Sean A. Grimm • Ann B. Ragin • James P. Chandler • Kenji Muro • Maryanne H. Marymont • Jeffrey J. Raizer Received: 17 October 2013 / Accepted: 18 February 2014 Ó Springer Science+Business Media New York 2014 Abstract Bevacizumab has been reported to cause diffu- sion restriction in the tumor bed of patients with malignant gliomas. This study evaluated prolonged diffusion restric- tion, in the corpus callosum (CC), of patients with malignant brain tumors treated with bevacizumab. We retrospectively reviewed our database of patients treated with bevacizumab for malignant brain tumors looking for those with restricted diffusion in the CC. CC ADC ratio measurements were obtained prior to and following treatment. Correlation was made with biopsy (n = 3) and MR perfusion (n = 7) and PET (n = 4). The temporal evolution of these changes rel- ative to therapy was examined with mixed effects regression analysis. Nine patients (eight malignant gliomas, one malignant meningioma) out of 146 patients were found to have developed areas of diffusion restriction in the CC. These areas tended to enlarge and coalesce over serial MRIs and persisted for up to 22 months. Hypoperfusion was demonstrated in MR perfusion in 7/7. PET was hypometa- bolic in all 4. Biopsy of the CC showed no tumor in 3/3. ADC ratio measurements indicated a significant overall effect of time (F(16,60) = 11.2; p \ 0.0001), consistent with per- sistent diffusion restriction over the measured time periods. Bevacizumab causes prolonged diffusion restriction in the CC. The negative MR perfusion, FDG PET and histopa- thology suggest this is a toxicity of bevacizumab and not active tumor. Awareness of these changes can assist in patient care. Keywords Bevacizumab Á Corpus callosum Á Toxicity Á Malignant glioma Introduction An important issue in imaging patients with malignant brain tumors is to distinguish recurrent tumor from post- treatment change [1–12]. The literature has focused on the spectrum of signal changes in the primary tumor bed using conventional, diffusion-weighted and advanced MR imaging techniques [2–8, 12]. Progress has been made in Stephen F. Futterer and Alexander J. Nemeth have contributed equally to this study. Poster presented at the Society of Neuro-Oncology Meeting, October 22–24, 2009, New Orleans, LA, under the title, ‘‘Novel MRI Changes in Patients on Bevacizumab.’’ S. F. Futterer Á A. J. Nemeth (&) Á A. B. Ragin Neuroradiology Section, Department of Radiology, Northwestern Memorial Hospital, Northwestern University, 676 N. Saint Clair St., Ste. # 1400, Chicago, IL, USA e-mail: anemeth@nmff.org S. A. Grimm Á J. J. Raizer Department of Neurology, Northwestern University, Chicago, IL, USA Present Address: S. A. Grimm Cadence Health, Winfield, IL, USA J. P. Chandler Á K. Muro Department of Neurosurgery, Northwestern University, Chicago, IL, USA Present Address: K. Muro Illinois Masonic Hospital, Chicago, IL, USA M. H. Marymont Department of Radiation Oncology, Northwestern University, Chicago, IL, USA 123 J Neurooncol DOI 10.1007/s11060-014-1409-2